In this R21 grant application we propose to conduct pilot work that will lay the foundation for a randomized clinical trial of bupropion SR to prevent smoking relapse in postpartum women. Although many women quit smoking during pregnancy, up to 70 percent are smoking again within one year of delivery. Behavioral interventions designed to prevent relapse following delivery have met with only limited success. At the same time, several trials have demonstrated that bupropion SR is safe and effective in promoting cessation. However, there are no published studies evaluating the effectiveness of bupropion SR in preventing relapse during particularly vulnerable periods, such as the postpartum period. Our ultimate goal is to evaluate the effectiveness of bupropion SR in preventing relapse during the postpartum period among women who quit smoking during pregnancy and are abstinent at the time of delivery through a double-blind, placebo-controlled, randomized clinical trial. This pilot study will allow us to develop and fine tune the methodology for the trial and demonstrate our ability to enroll and follow participants. In this study, we will enroll 50 women at the time of delivery and randomly assign them to receive placebo or bupropion SR for 12 weeks. Our objectives are to: a) test protocols for recruitment, sample collection, and follow-up; b) develop survey instruments; c) evaluate patient compliance; and d) estimate eligibility, participation, and retention rates for the larger trial. Patients and investigators will be blind to treatment assignment. Subjects in the treatment group will receive 300mg bupropion SR (150mg QD am for 7 days followed by 150mg BID for 11 weeks). Subjects in the control group will receive placebo following the same schedule. Both groups will receive 5 telephone-counseling sessions to encourage the maintenance of cessation in accordance with clinical practice guidelines. Patient compliance will be measured using the MEMS Track CapTM (Aprex Corporation, Union City, CA), which records each time and date the medication bottle is opened. Self-reported smoking status will be validated with a urine cotinine dipstick (<=100ng/ml) at baseline and saliva cotinine (<=30ng/ml) at 12 and 26 weeks postpartum. Data on covariates and mediating factors known to be associated with smoking cessation and relapse will be collected at baseline, week 12 and week 26 through telephone interviews. If proven effective in a follow-up randomized trial, the enrollment and implementation strategies we are testing could be utilized to implement a county or state program.